Smart Sonoafterglow Nanobombs for High-Contrast Imaging and Synergistic Gas-Sonodynamic Therapy of Hypoxic Tumors

Precise diagnosis and effective eradication of hypoxic tumors remain formidable challenges in cancer therapy. Here, we report a smart sonoafterglow nanobomb (TCL NPs) featuring a single US-triggered dual-activation mechanism for ONOO^--activated afterglow imaging and CO-gas potentiated sonodynamic therapy (SDT). TCL NPs are engineered from a sonosensitizer (TTQ), an ONOO^--responsive chemiluminescent substrate (CL─COOCH₃), and a ROS-activated CO prodrug (DHF). Upon ultrasound irradiation, TTQ generates ROS that oxidize CL─COOCH₃, triggering a bright near-infrared afterglow via chemiluminescence resonance energy transfer (CRET) for high-contrast, real-time tumor visualization. Simultaneously, the generated ROS induce CO release from DHF prodrug, which effectively alleviates tumor hypoxia and potentiates SDT efficacy. Due to this dual-activation mechanism, TCL NPs achieve precise ONOO^--sensitive imaging, robust tumor suppression, and potent induction of immunogenic cell death in vivo. Overall, unlike prior approaches that address either tumor imaging or hypoxia modulation alone, this work establishes a versatile sonoafterglow nanobomb for oxygen-independent, image-guided, and synergistic tumor theranostics.